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Benazeprilat (formerly known as CGS-14831), the active metabolite of the benazepril, is a potent inhibitor of angiotensin converting enzyme (ACE) with IC50 of 0.28 nM in plasma from dog.
Physicochemical Properties
| Molecular Formula | C22H24N2O5 |
| Molecular Weight | 396.443 |
| Exact Mass | 396.169 |
| CAS # | 86541-78-8 |
| Related CAS # | Benazeprilat-d5;1279033-05-4 |
| PubChem CID | 5463984 |
| Appearance | White to off-white solid powder |
| Density | 1.34 g/cm3 |
| Boiling Point | 711.3ºC at 760 mmHg |
| Melting Point | 270-272ºC |
| Flash Point | 384ºC |
| Index of Refraction | 1.643 |
| LogP | 2.55 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 29 |
| Complexity | 590 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | C(N1C(=O)[C@@H](N[C@H](C(=O)O)CCC2C=CC=CC=2)CCC2C=CC=CC1=2)C(=O)O |
| InChi Key | MADRIHWFJGRSBP-ROUUACIJSA-N |
| InChi Code | InChI=1S/C22H24N2O5/c25-20(26)14-24-19-9-5-4-8-16(19)11-13-17(21(24)27)23-18(22(28)29)12-10-15-6-2-1-3-7-15/h1-9,17-18,23H,10-14H2,(H,25,26)(H,28,29)/t17-,18-/m0/s1 |
| Chemical Name | (2S)-2-[[(3S)-1-(carboxymethyl)-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]amino]-4-phenylbutanoic acid |
| Synonyms | Benazeprilat CGS 14831 CGS-14831 CGS14831 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vivo | A good antihypertensive effect can be achieved by combining benazeprilat (10 mg/kg, intravenous injection) with amlodipine (0.5 mg/kg, intravenous injection) [2]. Oral benazepril (0.7 mg/kg) dramatically alters the kinetics of the systemic RAAS peptide, leading to a marked reduction in AII and ALD and an increase in PRA and AI [3]. |
| Animal Protocol |
Animal/Disease Models: Male SHR (14-16 weeks old, 250-350 grams) [2]. Doses: 10 mg/kg Route of Administration: IV; one time/day for 2 days Experimental Results: A hypotensive effect occurs. Animal/Disease Models: Beagle dog (12.0-19.5 kg) [3]. Doses: 0.7 mg/kg Route of Administration: Orally, one time/day for 5 days. Experimental Results: Effects of systemic RAAS peptides. |
| References |
[1]. Barrios V, Antihypertensive and organ-protective effects of benazepril. Expert Rev Cardiovasc Ther. 2010 Dec;8(12):1653-71. [2]. Bazil MK, Hemodynamic effects of amlodipine and benazeprilat in spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1993 Mar;21(3):405-11. [3]. Mochel JP, Capturing the dynamics of systemic Renin-Angiotensin-Aldosterone System (RAAS) peptides heightens the understanding of the effect of benazepril in dogs. J Vet Pharmacol Ther. 2013 Apr;36(2):174-80. |
| Additional Infomation |
Benazeprilat is a benzazepine that is 1,3,4,5-tetrahydro-2H-1-benzazepin-2-one in which the hydrogen attached to the nitrogen is replaced by a carboxy methyl group and in which the 3-pro-S hydrogen is replaced by the amino group of (2S)-2-amino-4-phenylbutanoic acid. An angiotensin-converting enzyme inhibitor, it is used as its monoester prodrug benazepril in the treatment of hypertension and heart failure. It has a role as an EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor. It is a benzazepine, a dicarboxylic acid and a lactam. Benazeprilat is an Angiotensin Converting Enzyme Inhibitor. The mechanism of action of benazeprilat is as an Angiotensin-converting Enzyme Inhibitor. The physiologic effect of benazeprilat is by means of Decreased Blood Pressure. Benazeprilat is the active metabolite of benazepril, a carboxyl-containing angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Once the prodrug benazepril is metabolized to benazeprilat in the liver, benazeprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II, resulting in vasodilation. Benazeprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow. See also: Benazepril Hydrochloride (active moiety of). |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5224 mL | 12.6122 mL | 25.2245 mL | |
| 5 mM | 0.5045 mL | 2.5224 mL | 5.0449 mL | |
| 10 mM | 0.2522 mL | 1.2612 mL | 2.5224 mL |